Chromatography Forum

As per ICH, Accuracy is being demonstrated by performing 3 replicates each of three separate sample concentrations.
Question:

Let say, I have an Assay Specification of 80% -120%, What would be the recommended criteria for its percent recovery (on Accuracy test). Does ICH has clear guideline on this?
Can I set it as 95% - 105% percent recovery?

Thanks.

That seems reasonable to me given your spec is relatively wide. The tightest I would set the accuracy limit is 97.0% to 103.0% for such a wide specification. Please made sure you take into consideration the potency of the drug and other variabilities e.g. other analytical method variabilities, potency loss on stability, and manufacturing variability.

ICH does not have a recommendation for accuracy recovery. I would let your prevalidation data drive your acceptance criterion for your protocol.

The two values interact. Logically, your product specification needs to be aware of your accuracy of measurement. The thinking should be like this:

(1) For the intended application of this product, a variation more than (for example) +/- 20% would be bad.
(2) Include a general safety-factor if desired. Maybe if 20% deviation has seriously bad consequences, we would prefer to reject product that deviates by more than 10%.
(3) If we think the analytical precision and accuracy allow a 5% error, then if we specify +/- 10%, a measurement of 10% could actually be as bad as 15%, so instead we should insist on a smaller analytical error-window such that analysis still guarantees that the product is within the safety-window we specified. Therefore if we want to guarantee +/- 10%, we can specify our product as +/- 10% if our analysis is perfect, or perhaps +/- 5% if it's not...

What accuracy and precision you get is going to depend on the instrument, the analyte, the level at which you're analysing etc. etc.; it has to be good enough for purpose, but for once I agree with ICH in not specifying a rigid number.